Sepsis 3 & Early Identification David Carlbom, MD Medical Director, HMC Sepsis Program Disclosures I have no relevant financial relationships with a commercial interest and will not discuss off-label use of a product or any investigational products. I do think systematic identification and rapid treatment of sepsis saves lives. Objectives Be able to discuss the definition Sepsis 3 Describe the importance of rapid identification Explain how the SePSIS early warning system can help identify sepsis patients Describe the challenges & opportunities of CMS Sepsis Core Measure 1
Sepsis is defined as lifethreatening organ dysfunction caused by a dysregulated host response to infection. Singer et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016 We have a definition for sepsis. Criteria for the bedside? Developing Bedside Criteria Use large electronic health record databases Identify those with suspected infection Study various existing organ dysfcn criteria SOFA score LODS score SIRS criteria 2
quick Sepsis - Related Organ Failure Assessmen qsofa.org qsofa as a clinical prompt Hypotension SBP 100 AMS GCS 13 Tachypnea RR 22 2 of 3 criteria ~10% mortality Developing Bedside Criteria Seymour et al. JAMA 2016 3
Baseline Risk at the Bedside Baseline risk model using only age, demographics, race, co-morbidity Divide patients into deciles 25 20 15 10 5 0 No. of patients Risk of in-hospital mortality 7,449 1 2 3 4 5 6 7 8 9 10 7,456 7,515 7,372 7,572 7,301 7,523 7,390 7,515 7,346 Deciles of baseline risk of in-hospital mortality Compare validity within and across deciles Seymour et al. JAMA 2016 Variable Threshold Units All patients (N=74,453) ICU patients (N=7,836) Non-ICU patients (N=66,617) Heart rate >90 BPM Respiratory rate >20 BPM SIRS variables Temperature <36 C White blood cell count >12 k/ul Temperature >38 C White blood cell count <4 k/ul Bands >10 % Systolic blood pressure <=100 mmhg Serum creatinine >=1.2 mg/dl Pa0 2 / Fi0 2 ratio <=300 SOFA variables Platelets <=150 k/ul Glasgow coma scale <15 Bilirubin >=1.2 mg/dl Mechanical ventilation Present/absent Vasopressors Present/absent Vasopressors More than one Bicarbonate <=26 mmol/l Saturation <=94 % Glucose <=109 mg/dl AST >=36 IU/L Additional candidate variables ALT >=37 IU/L INR >=1.4 Albumin <=2.5 g/dl Troponin >=0.1 ng/ml ph <=7.36 Lactate >=2.5 mmol/l Fibrinogen <=300 mg/dl ScvO 2 <=69 % Abnormal Normal Missing 0 50 100 0 50 100 0 50 100 Proportion (%) Proportion (%) Proportion (%) Seymour et al. JAMA 2016 Predictive validity of criteria: ICU Fold change, in-hospital mortality 10000 1000 100 10 1 0.1 Baseline risk (%) ICU encounters N = 7,932 SIRS 2 vs. SIRS <2 SOFA 2 vs. SOFA <2 LODS 2 vs. LODS <2 qsofa 2 vs. qsofa <2 1 2 3 4 5 6 7 8 9 10 Decile of baseline risk of in-hospital mortality Seymour et al. JAMA 2016 4
Predictive validity of criteria: non- ICU 10000 SIRS 2 vs. SIRS <2 SOFA 2 vs. SOFA <2 1000 ICU encounters N = 7,932 LODS 2 vs. LODS <2 qsofa 2 vs. qsofa <2 100 10 1 0.1 Baseline risk (%) 1 2 3 4 5 6 7 8 9 10 Fold change, in-hospital mortality Decile of baseline risk of in-hospital mortality Seymour et al. JAMA 2016 Test Performance SIRS 0.64 (0.62, 0.66) ICU encounters N = 7,932 AUROC in-hospital mortality SIRS 0.76 (0.75, 0.77) Outside the ICU encounters N = 66,522 AUROC in-hospital mortality SOFA <0.01 0.74 (0.73, 0.76) SOFA <0.01 0.79 (0.78, 0.80) LODS <0.01 0.20 0.75 (0.73, 0.76) LODS <0.01 <0.01 0.81 (0.80, 0.82) qsofa 0.01 <0.01 <0.01 0.66 (0.64, 0.68) qsofa <0.01 <0.01 0.72 0.81 (0.80, 0.82) SOFA and LODS superior in the ICU qsofa similar to complex scores outside the ICU qsofa in external datasets Seymour et al. JAMA 2016 5
SOFA SOFA Lactate Proportion in hospital mortality (%) 100 80 60 40 20 0 Missing qsofa = 0 qsofa = 1 qsofa = 2 qsofa = 3 < 2.0 mmol/l 2.0 to 4.0 mmol/l Serum lactate 4.0 mmol/l 6
Who is really, really, really sick? Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality Shankar-Hari et al, JAMA 2016 Septic Shock Grou p Hypotension p Fluids Vasopress or Lactate >2mmol/L Hospital Mortality 1 Yes Yes Yes 42.3% 2 Yes Yes No 30.1% 3 Yes No Yes 28.7% 4 No No Yes 25.7% 5 No hypotension before No Yes 29.7% 6 Yes No No 18.7% Shankar-Hari et al, JAMA 2016 Septic Shock Sepsis with persisting hypotension requiring vasopressors to maintain MAP 65 mmhg Serum lactate level >2 mmol/l Despite adequate volume resuscitation Shankar-Hari et al, JAMA 2016 7
2003 vs 2016 Definitions Sepsis Severe Sepsis Septic Shock 2003 2016 Suspected Infection + 2/4 SIRS Criteria Sepsis + Organ Dysfunction (variably defined) Sepsis + Hypotension despite adequate fluid resus Delta SOFA 2 OR qsofa 2 N/A Sepsis + Vasopressors needed MAP>65 + Lactate > 2 despite adequate fluid resus What Next? SSC new guidelines targeted for Fall 2016 release CMS is not changing to new definition Don t let naming your patient prevent good, prompt care of infection and organ dysfunction OK, How about 2am? Start with SIRS Treat Infection Abx without delay 30mL/kg volume qsofa = 10% mort. SOFA qsofa.org 8
OK, How about 2am? Start with SIRS Treat Infection Abx without delay 30mL/kg volume qsofa = 10% mort. SOFA CMS Measure SEP-1 Beginning 10/1/2015 discharges First year data gathering (refining criteria?) TBD: becomes part of Value Based Purchasing CMS Definitions 9
CMS Definitions 3 hour bundle Sepsis 3 hour bundle: Measure lactate Obtain blood cultures Administer antibiotics 30 ml/kg crystalloids 6 hour (shock) Bundle Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) 65 mm Hg In the event of persistent hypotension after initial fluid administration (MAP < 65 mm Hg) or if initial lactate was 4, re-assess volume status and tissue perfusion and document findings Re-measure lactate if initial lactate elevated 10
Volume Re-assessment Volume Re-assessment 11
Screening at HMC 1. QSD Monitors SIRS Score 2. QSD Triggers Screening Order/Task 3. RN Completes Screening PowerForm 4a. RN Gets Immediate Feedback 7. Screening and Follow-up Documentation Adjust Trigger Criteria 6. RN Completes Follow-up PowerForm 5. QSD Triggers Follow-up Order/Task 4b. Page Sent to Care Team 12
Sepsis Classification 15% 4% Sepsis 3% 43% 35% Severe Sepsis Septic Shock Septic Shock POA Septic Shock Dx in ICU Screening Performance Value C.I. Sensitivity 89% 85.7% - 91.3% Specificity 51% 48.8% - 53.2% Positive Predictive Value Negative Predictive Value 31.6% 29.2% - 34.1% 94.7% 93.2% - 95.9% Antibiotic Timing & Survival Septic Shock Kumar CCM 2006 13
Severe Sepsis Hospital Mortality Surviving Sepsis cohort 17,990 patients with severe sepsis Adjusted by severity, admit source, geography Adjusted Mortality Ferrer CCM 2014 Early Fluid Survivors Non-survivors p IVF in First 3 hours 2085 ml 1600 ml 0.007 IVF in Hour 3.1-6 660 ml 880 ml 0.09 Total IVF in 6 hours 3150 ml 2875 ml 0.1 higher proportion of fluid <3 hours associated with lower mortality OR 0.34 (95% CI, 0.15-0.75) Lee Chest 2014 Vasopressor Timing Septic Shock Patients Time to Norepinephrine 5.3% increase in mortality for every hour delay after 2 hours Bai, CritCare 2014 14
RN-driven Care RN notifies MD Draws lactate Draws cultures Initiates 500mL bolus 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% % Pts Meeting Goal 48% 81% 56% 12% 80% 36% Lactate Abx < 1hr Fluids 30mL/kg Coates, J Hosp Med 2015 Summary Seek out Sepsis & Infection Recognize SIRS is sensitive, may find earlier than qsofa Design a standard method for rapid assessment Care team huddle, Could this be sepsis? 15